Research Summary:

Dr. Hetrick's research focuses on brain-behavior relationships in psychopathology,
including schizophrenia, bipolar disorder, and autism.

SENSORY GATING

One compontent of Dr. Hetrick's research investigates the origins and
correlates of perceptual, attentional, and cognitive aberrations in schizophrenia
and related psychotic disorders. Sensory gating hypotheses assert that
these aberrations arise from deficits in gating, or filtering, or exteroceptive
input by the central nervous system. It is speculated that this inability
to gate or filter sensory inputs underlies information processing deficits
- such as hyper-vigilance and poor selective attention - and might contribute
to a psychotic state in which patients with schizophrenia are disorganized
by an overabundance of irrelevant sensory stimulation. In other words,
inundation of the central nervous system by irrelevant inputs may disrupt
ongoing cognitive processes, resulting in cognitive fragmentation and
disorganization. Dr. Hetrick's laboratory is examining this process, termed
sensory gating, across levels of analysis, including both neurophysiological
and phenomenological/symptom levels.

TEMPORAL PROCESSING DYSFUNCTIONS IN SCHIZOPHRENIA

Another line of research concerns deficits in the temporal coordination
of information processing throughout the brain in schizophrenia. Much
research to date into the causes of schizophrenia has focused on identifying
the structures in the brain that give rise to the disorder. In contrast,
Dr. Hetrick's research examines the extent to which impairments in the
timing of neural responses and time-dependent communications between brain
areas underlie schizophrenia. Dr. Hetrick's functional, rather than strictly
structural approach, hypothesizes that neurons in the brain do not appropriately
synchoronize their activity with each other. In turn, neural centers in
the brain, referred to as nuclei, fail to encode, manipulate, and pass
along information in a timely manner. These failures cause inconsistent
interactions in time between neural centers, which may impair perceptual,
affective, cognitive, and motor processes; widespread failures of this
sort may lead to disturbances of consciousness which characterize schizophrenia.
This work began with the previously mentioned observation of within-subject,
trial-by-trial P50 peak latency variability in schizophrenia, which suggested
a neural deficit in response timing and neural synchrony (Jin et al.,
1998; Patterson et al., 2000).

There is accumulating theoretical and empirical support for the hypothesis
that schizophrenia is associated with a fundamental disturbance in the
timing of neural processes (Andreasen et al., 1998; Tononi & Edelman,
2000; Paulus & Braff, 2003; Phillips & Silverstein, 2003). Deficites
in the temporal coordination of information processing in the brain may
lead to disturbances of consciousness as well as poor coordination of
perceptual, affective, cognitive, and motor processes similar to classic
symptoms of schizophrenia such as thought disorder, and disorganized and
contextually inappropriate behavior (Andreasen et al., 1998). Support
for these conceptualizations is emerging with evidence that brain structures
(e.g., cerebellum & basal ganglia) and neurotransmitter systems (e.g.,
dopamine & glutamate) that are directly linked to neural timing processes
are also impaired in schizophrenia. Andreasen and her colleagues (1998)
conceptually organized some of these theories and findings by suggesting
that "cognitive dysmetria," or poor coordination of cognitive
processes, is a fundamental problem in schizophrenia. Andreasen postulated
that a cortico-cerebellar-thalamic-cortical (CCTC) brain circuit - believed
to be responsible for fluid, temporal coordination of sequences of behavior
- is a likely source of timing anomalies. This conceptualization is intriguing
given the evidence for the essential role of cerebellum in cognitive and
affective functions (e.g., Leiner et al., 1993; Schmahmann, 2001), and
is being rigorously examined in my laboratory. Dr. Hetrick is examining
the functional integrity of neural timing circuits in schizophrenia using
three well-estabished timing tasks: eye-blink conditioning (EBC), time
estimation (e.g., temporal bisection task), and time production and reproduction
(e.g., free and paced finger tapping).

ERROR-RELATED NEGATIVITY, TASK SWITCHING, AND THE COMORBIDITY
OF SCHIZOPHRENIA AND ALCOHOL DEPENDENCE

In view of the fact that schizophrenia is associated with multiple information
processing deficits, Dr. Hetrick employs several other electrophysiological
indices tailored to the study of higher-order cognitive functioning. One
of these indices, referred to as error-related negativity (ERN), assesses
the ability of the brain to monitor its output and very quickly detect
response errors. Another of these indices, referred to as the P300 brainwave,
assesses the brain's ability to identify task-relevant stimulus cues in
the environment and switch the focus attention between cues to maximize
performance in a dynamic task. In addition, Dr. Hetrick is studying the
comorbidity of schizophrenia with alcohol dependence in an effort to determine
shared and unique electrophysiological endophenotypes, or neurobiological
markers, that may contribute to their comorbidity; this work is funded
by a grant from the National Institute of Mental Health (NIMH).